Time to embrace sepsis pathways and antibiotic prescribing decision support in the emergency department: Observations from a retrospective single site clinical audit.

Objective: To compare clinician documentation of sepsis for infective presentations in the ED against a formal sepsis pathway in the ED and to assess appropriateness of the initial parenteral antibiotic prescription for adult patients in ED.

Methods: A retrospective, clinical audit of adult patients who received at least one parenteral antibiotic in ED over a 10-week period in 2018. Documented initial clinical impression was compared with an approved sepsis pathway.

Feasibility and safety of targeting the anterior superior iliac spine to perform a bone marrow procedure: a prospective, clinical study.

Aims: The bone marrow procedure (BMP) has been performed worldwide for years. Nonetheless, no generally accepted standards or guidelines for the performance of the BMP exist. Recent studies suggested that the lateral angulation technique (LAT), targeting the anterior superior iliac spine (ASIS) after penetration of the posterior superior iliac spine, yields longer biopsy cores and is safer for patients.

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited.

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

Objectives: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants.

Experimental Design: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity.

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

Objective: Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB.

Research Design And Methods: Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order.

Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.

Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution.

The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development.

Acquired Von Willebrand's Syndrome in Systemic Lupus Erythematosus.

Acquired von Willebrand syndrome (AVWS) is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE) is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca.

Safe and successful bone marrow biopsy: an anatomical and CT-based cadaver study.

Bone marrow biopsy is generally a safe procedure. However, infrequently the procedure is associated with serious injuries that are attributed to inadvertent needle penetration of the iliac bone's inner cortex. An evidence-based approach to needle orientation during iliac crest biopsy does not exist.

Ageing diminishes the modulation of human brain responses to visual food cues by meal ingestion.

Background/objectives: Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised.

The OnControl bone marrow biopsy technique is superior to the standard manual technique for hematologists-in-training: a prospective, randomized comparison.

The purpose of this study was to compare a novel bone marrow device with the standard marrow needle in a prospective, randomized study in a teaching hospital employing hematologists-in-training. The new device, the OnControl Bone Marrow (OBM) Biopsy System, utilizes a battery-powered drill to insert the needle. Fifty-four bone marrows (27 standard and 27 OBM) were performed by 11 fellows under the observation and supervision of 3 attending hematologists and 1 research technologist.

Regional cerebral blood flow and FDG uptake in asymptomatic HIV-1 men.

Despite advances in the treatment of patients with human immunodeficiency virus (HIV), HIV-associated neurocognitive disorder occurs in 15-50% of HIV-infected individuals, and may become more apparent as ageing advances. In the present study we investigated regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose uptake (rCMRglc) in medically and psychiatrically stable HIV-1-infected participants in two age-groups. Positron emission tomography (PET) and magnetic resonance imaging (MRI)-based arterial spin labeling (ASL) were used to measure rCMRglc and rCBF, respectively, in 35 HIV-infected participants and 37 HIV-negative matched controls.

Endogenous opioid release in the human brain reward system induced by acute amphetamine administration.

Background: We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET).

Methods: Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin.

The response to rapid infusion of fentanyl in the human brain measured using pulsed arterial spin labelling.

Objective: We evaluated the sensitivity of pulsed Arterial Spin Labelling (pASL) for the detection of changes in regional cerebral blood perfusion (CBP) during and after intra-venous (i.v.) infusion of an opioid agonist (fentanyl) and an opioid antagonist (naloxone).

GABAB receptors in addiction and its treatment.

The GABA(B) receptor plays an important role in the control of neurotransmitter release, and experiments using preclinical models have shown that modulation of this receptor can have profound effects on the reward process. This ability to affect the reward process has led to clinical investigations into the possibility that this could be a viable target in the treatment of addiction. Presented here is an overview of a number of studies testing this hypothesis in different drug dependencies.

Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.

The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers.

Nicotine dependence is characterized by disordered reward processing in a network driving motivation.

Background: Drug addiction is characterized by an unhealthy priority for drug consumption with a compulsive, uncontrolled drug-intake pattern due to a disordered motivational system. However, only some individuals become addicted, whereas others maintain regular but controlled drug use. Whether the transition occurs might depend on how individuals process drug relative to nondrug reward.

Changes in neuropsychological functioning during alcohol detoxification.

This study investigates changes in neuropsychological functioning during early abstinence from alcohol. 30 alcohol-dependent inpatients were tested at intake (day 4 of admission) and post detoxification (day 26), using a test-retest design. The neuropsychological battery included measures of pre-morbid IQ, full-scale IQ, verbal and non-verbal measures of memory and executive function.

Hemisphere-specific episodic memory networks in the human brain: a correlation study between intracarotid amobarbital test and [(18)F]FDG-PET.

The purpose of the present study was to explore the brain regions involved in human episodic memory by correlating unilateral memory performance estimated by the intracarotid amobarbital test (IAT) and interictal cerebral metabolism measured by [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET). Using this method, regional alterations of cerebral metabolism associated with epilepsy pathophysiology are used to predict hemisphere-specific episodic memory function, hence, investigate the differential distribution of memory in each hemisphere. Sixty-two patients with unilateral temporal lobe epilepsy (35 left and 27 right) were studied using [(18)F]FDG-PET with complementary voxel-based statistical parametric mapping (SPM) and region-of-interest (ROI) methods of analysis.

Attenuation of amydgala and frontal cortical responses to low blood glucose concentration in asymptomatic hypoglycemia in type 1 diabetes: a new player in hypoglycemia unawareness?

Objective: Loss of ability to recognize hypoglycemia (hypoglycemia unawareness) increases risk of severe hypoglycemia threefold in insulin-treated diabetes. We set out to investigate the cerebral correlates of unawareness in type 1 patients.

Research Design And Methods: Regional changes in brain glucose kinetics were measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), in 13 men with type 1 diabetes--6 with hypoglycemia awareness and 7 with hypoglycemia unawareness--at euglycemia (5 mmol/l) and hypoglycemia (2.

Comparison of buprenorphine and methadone in the treatment of opiate withdrawal: possible advantages of buprenorphine for the treatment of opiate-benzodiazepine codependent patients?

The study is a preliminary investigation to compare the effectiveness of buprenorphine and methadone as opiate detoxification treatments. The sample comprised 123 drug misusers who were dependent upon opiates only or who were codependent upon opiates and benzodiazepines. Drug misusers dependent upon methadone doses up to 70 mg were eligible for the study.